Beta-Propiolactone (BPL) is a monofunctional direct-acting alkylating agent which is carcinogenic in mice and rats by various routes of administration. Earlier studies on its mode of action have dealt with its reactions with mouse skin DNA and RNA. However, few reports have dealt with the interaction of BPL with histones and nonhistone chromatin proteins. The studies proposed in this application will deal with the in vitro and in vivo reactions of BPL with histones and nonhistone chromatin proteins in whole mouse skin chromatin. These studies will focus on the determination of the amino acids containing bound BPL and the specificity of BPL-binding among the various protein fractions. The manner in which BPL-alkylation of DNA affects the binding of chromatin proteins to such DNA and the structure determination of a new BPL-alkylated base from mouse skin DNA will be determined. Studies will also be conducted to determine whether BPL binds to phosphate groups of DNA by investigating reactions between BPL and model nucleotides. The chromatin proteins are regulators of gene activity in cells and a knowledge of the mode and specificity of carcinogen binding to these proteins and the other proposed studies will contribute to an understanding of the basic mechanisms of action of direct-acting alkylating carcinogens.